A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

Abstract

Olfactory receptors (ORs) are expressed and active in various human tissues, including the skin. Although the sense of smell plays an important physiological role in the regulation of mood and stress, a link between olfactive compounds, ORs, and skin stress has yet to be established. This study aims to investigate the role of newly identified skin ORs and agonists in the modulation of skin stress. Screening for odorant molecules was done with cAMP functional assay to identify OR agonists. RT-qPCR and immunofluorescence microscopy were conducted to identify and quantify ORs in epidermal keratinocytes (NHEKs) and human skin explants, as well as to evaluate specific markers (G6PDH, loricrin, and γH2AX) of stress-induced skin alterations. A randomized double-blinded, split-face clinical study was performed on a panel of stressed women to measure the benefits of OR agonist treatment for skin. Three new ORs (OR10A6, OR2AG2, and OR11H4) were identified in skin. A specific Rose extract and its major constituent (phenylethyl alcohol) were found to activate these ORs. The extract composition was revealed by both GC/FID and GC/MS analyses simultaneously and showed the presence of 34 volatiles molecules. Moreover, epinephrine induces a skin stress response characterized by increased expression of G6PD, loricrin, and γH2AX biomarkers, and a decrease of OR expression. These effects were prevented in the presence of rose extract and its benefits were confirmed clinically by a decrease in the appearance of under-eye dark circles. Altogether, our findings suggest that ORs may represent a new, promising way to treat stress-associated skin disorders.

Mutated genes on ctDNA detecting postoperative recurrence presented reduced neoantigens in primary tumors in colorectal cancer cases

“…In CRCR1P, mutated OR10A6 showed a higher binding affinity (20 [5.29%] of 378 peptides) to HLA than that of other mutated genes (p < 0.0001). On the other hand, the mutated OR10A6 gene was not presented as a neoantigen (Table 2 ); therefore, OR10A6 18 must not be presented as a neoantigen peptide. As shown in Table 2 , representative mutated genes that could be chronologically traced by ctDNA showed either low binding affinities with HLA or low expression of mutated genes in a mutually exclusive manner.…”

α-ionone promotes keratinocyte functions and accelerates epidermal barrier recovery

“…Furthermore, its stimulatory effects on cell proliferation, migration, and gene expression of HAS2/3 and HBD-2 were all abrogated by the cAMP inhibitor, indicating that the α-ionone-induced activation of the cAMP signaling pathway is required for the beneficial effects of α-ionone on HaCaT cells. Although the mechanisms of how α-ionone increases intracellular cAMP levels remain unknown, it is noteworthy that α-ionone was recently identified as an agonist for 2 ORs, namely OR51E2 and OR10A6 ( 61 , 62 ). As these ORs have been detected to be expressed in human keratinocytes ( 62 ), it is quite possible that one or both may participate in the α-ionone-induced increase in cAMP levels.…”

“…Although the mechanisms of how α-ionone increases intracellular cAMP levels remain unknown, it is noteworthy that α-ionone was recently identified as an agonist for 2 ORs, namely OR51E2 and OR10A6 ( 61 , 62 ). As these ORs have been detected to be expressed in human keratinocytes ( 62 ), it is quite possible that one or both may participate in the α-ionone-induced increase in cAMP levels. Additional studies are needed to evaluate this possibility.…”

The human odorant receptor OR10A6 is tuned to the pheromone of the commensal fruit fly Drosophila melanogaster

“…In vitro screening showed that the functional variant of OR10A6, which ranks among the most highly transcribed ORs in the olfactory epithelium ( Saraiva et al., 2019 ; Verbeurgt et al., 2014 ), is most sensitively tuned to Z4-11Al. OR10A6 may also be tuned to other odorants, such as cyclamen aldehyde ( Duroux et al., 2020 ), and further experiments are needed to map its entire agonist space.…”